Two-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration with 'observe before treat-and-extend' method.

Purpose: To evaluate two-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with 'observe before treat-and-extend' (O-TAE) strategy in the real-world setting. Methods: This retrospective study included treatment-naïve nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after 3 monthly loading injections. In case of recurrence, treatment was resumed using the treat-and-extend (TAE) regimen starting from the 4th injection. In case of non-recurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following 3 loadings were analyzed. Results: 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logMAR improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the 1st year (p = 0.01), and 0.25 ± 0.22 in the 2nd year (p = 0.054). CMT decreased significantly from 357.4 ± 74.5 at baseline to 269.6 ± 48.1 in the 1st year (p < 0.001), and 279.1 ± 54.6 in the 2nd year (p < 0.001). Numbers of injections were 5.1 ± 1.7 in the first year and 3.8 ± 2.4 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after 3 loadings, 28 eyes (78%) recurred, and the average period of recurrence was 6.5 months. The remaining 8 eyes (22%) had no recurrence during the mean follow-up period of 29.7 months. Conclusion: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

Repeatability and Agreement of Chord Mu between Scheimpflug Tomography and Swept-Source Optical Coherence Tomography.

PURPOSE: To evaluate repeatability and agreement of chord mu between Scheimpflug tomography (Pentacam HR) and sweptsource optical coherence tomography-based optical biometer (IOLMaster 700). METHODS: In this retrospective study, 63 eyes from 33 patients were included. Chord mu, X and Y Cartesian distances between the corneal vertex and the pupil center (Px and Py), and the pupil diameter were compared using two instruments. Repeatability was evaluated using intraclass correlation coefficient (ICC), coefficient of variation (CoV), and within-subject standard deviation (Sw). Interdevice agreement was evaluated using paired t-tests and Bland-Altman plots. RESULTS: Although Sw values for all parameters were similar between the two devices, CoV values of chord mu and pupil diameter were lower, and ICC values of those parameters were higher, in the IOLMaster 700 than in the Pentacam HR. Chord mu and pupil diameter values were higher in IOLMaster 700 than Pentacam HR (p < 0.01). The width of the 95% limit of agreement was wide for all parameters. CONCLUSIONS: IOLMaster 700 showed better repeatability than Pentacam HR in chord mu, Px, Py, and pupil diameter values. Because there were statistically significant differences and a low level of agreement in chord mu and pupil diameter values between the two devices, they cannot be used interchangeably.

Discontinuation of treatment and retreatment of neovascular age-related macular degeneration in the real-world: Bundang AMD cohort study report 5.

Introduction: This single-center retrospective cohort study investigated the incidence rate and risk factors for the discontinuation of anti-vascular endothelial growth factor (VEGF) injections and retreatment in typical neovascular age-related macular degeneration (tnAMD) and polypoidal choroidal vasculopathy (PCV) in the real-world setting. Methods: A total of 488 eyes with either tnAMD (n = 334) or PCV (n = 154) followed up for ≥3 years were analyzed. The discontinuation of treatment was defined as the cessation of anti-VEGF injections for 1 year or longer. Eyes with discontinuing treatment were subdivided into group A: eyes with stable responses (complete or incomplete resolution) and group B: those with no expectation of visual gain or poor response. The proportion and median time of discontinuation of treatment or retreatment were analyzed. The visual prognosis and the associated risk factors for the discontinuation of treatment or retreatment were also investigated. Results: The mean follow-up period was 8.1 ± 3.4 years. Of 488 eyes, discontinuation of the treatment occurred in 322 eyes (66.0%), and the median time to discontinuation was 1.5 years after the initial injection. Of 297 eyes with discontinuation of treatment excluding 25 eyes with vitrectomy or photodynamic therapy after the discontinuation of the injection, 277 eyes belonged to group A and the remaining 20 eyes belonged to group B. Of the 277 eyes discontinuing treatment with a stable response, 185 eyes (66.8%) were given retreatment. The median time to retreatment was 3.3 years after the discontinuation of the injections. PCV and the lower annual number of injections were the significant factors associated with discontinuation. Younger age, male gender, and PCV were the significant factors for the retreatment. Conclusion: Our long-term real-world study showed that two-thirds of eyes with neovascular age-related macular degeneration (nAMD) had the discontinuation of the anti-VEGF injections and two-thirds of eyes discontinuing treatment with stable responses experienced retreatment. Long-term follow-up and regular monitoring are needed to detect the recurrence.

Agreement between Two Swept-Source Optical Coherence Tomography Biometers and a Partial Coherence Interferometer.

PURPOSE: To evaluate the level of agreement between ANTERION (Heidelberg Engineering, Heidelberg, Germany), OA-2000 (Tomey, Nagoya, Japan), and IOLMaster 500 (Carl Zeiss AG, Jena, Germany). METHODS: Fifty-one eyes of 51 patients were included in the study. Flat keratometry (K) and steep K, vector component of astigmatism (Jackson cross-cylinder at 0° and 90° [J0] and Jackson cross-cylinder at 45° and 135° [J45]), anterior chamber depth, and axial length were compared using the three devices. Repeated measures analysis of variance was conducted to compare the mean values of the biometrics. Pearson correlation test was conducted to analyze the correlations of the measured values, and a Bland-Altman plot was used to assess the agreement between the three devices. The predicted intraocular lens power of each device was compared to the others using the SRK/T, Haigis, Barrett Universal II, and Kane formulas. RESULTS: All K values measured using ANTERION were flatter than those of other instruments. However, good agreement was observed for flat K (ANTERION - OA-2000; 95% limits of agreement [LoA], 0.86 diopters [D]) and steep K (ANTERION - OA2000; 95% LoA, 0.93 D) and OA-2000 - IOLMaster 500 (95% LoA, 0.93 D). J0 and J45 vector components of astigmatism were not statistically different; however, the agreements were poor between the devices (95% LoA ≥1.97 D). Anterior chamber depth values of ANTERION and OA-2000 were interchangeable (95% LoA, 0.15 mm). The axial length showed a high agreement (95% LoA ≤0.17 mm) among the three devices. The predicted intraocular lens powers of the three devices were not interchangeable regardless of formulas (95% LoA ≥1.04 D). CONCLUSIONS: Significant differences in ocular biometrics were observed between ANTERION and the other two devices. This study demonstrated that only axial length showed good agreement among devices.

Massive submacular haemorrhage in polypoidal choroidal vasculopathy versus typical neovascular age-related macular degeneration.

PURPOSE: To investigate the incidence rate of massive submacular haemorrhage (SMH) and risk factors in polypoidal choroidal vasculopathy (PCV) and typical neovascular age-related macular degeneration (tnAMD). METHODS: A total of 465 patients who were diagnosed with either PCV (n = 245) or tnAMD (n = 220) from 2003 to 2014 were enrolled. Cumulative incidence of massive SMH in PCV and that in tnAMD were compared. Risk factors of massive SMH were also analysed. RESULTS: Massive SMH occurred in 32 patients (13.1%) with PCV and 9 patients (4.1%) with tnAMD. Incidence rates of massive SMH 5 and 10 years after the first visit were 11.1% and 29.9% in PCV and 4.3% and 9.9% in tnAMD, respectively. Incidence rates of massive SMH in PCV were significantly higher than those in tnAMD (hazard ratio [HR], 2.66; p = 0.007). Cox regression analysis revealed that mean number of photodynamic therapies (PDTs) per year (HR, 4.24; p < 0.001), cluster type of polypoidal lesion (HR, 3.42; p = 0.003) in PCV, and mean number of anti-VEGF injections per year (HR, 1.58; p < 0.001) in tnAMD were significantly associated with risk of massive SMH. For patients with severe vision loss, proportion of incident massive SMH was significantly higher in PCV (29.5%) than in tnAMD (6.9%, p < 0.001). CONCLUSION: The incidence rate of massive SMH in eyes with PCV was about three times higher than that in eyes with tnAMD. Treatment methods that can reduce the incidence of massive SMH should be considered, especially for eyes with PCV.

Association of Irregular Pigment Epithelial Detachment in Central Serous Chorioretinopathy with Genetic Variants Implicated in Age-related Macular Degeneration.

We evaluated phenotype and genotype correlation of central serous chorioretinopathy (CSC) patients with or without irregular pigment epithelial detachment (PED) on optical coherence tomography (OCT). For CSC, a flat, irregular protrusion of retinal pigment epithelium (RPE) with hyper-reflective sub-RPE fluid on OCT was defined as an irregular PED. Participants were classified into 5 subgroups; (1) total CSC (n = 280) (2) CSC with irregular PED (n = 126) (3) CSC without irregular PED (n = 154) (4) typical choroidal neovascularization (CNV) (n = 203) and (5) polypoidal choroidal vasculopathy (PCV) (n = 135). Ten known major AMD-associated single-nucleotide polymorphisms (SNPs) were analyzed. Age, sex adjusted logistic regression was performed for the association between subgroups. Association analysis between CSC without irregular PED and CNV revealed that significant difference for rs10490924 in ARMS2, rs10737680 in CFH, and marginally significant difference for rs800292 in CFH. Between CSC without irregular PED and PCV, rs10490924, rs10737680, and rs800292 were significantly different. In contrast, CSC with irregular PED and CNV revealed no SNP showing significant difference. Between CSC with irregular PED and PCV, only rs10490924 was significantly different. CSC with irregular PED and CSC without irregular PED revealed significant difference for rs800292, and marginal difference for rs10737680. These findings suggest CSC patients with irregular PED are genetically different from those without irregular PED and may have genetic and pathophysiologic overlap with AMD patients.

POSTTREATMENT POLYP REGRESSION AND RISK OF MASSIVE SUBMACULAR HEMORRHAGE IN EYES WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To study the association between the risk of massive submacular hemorrhage (SMH) and polyp regression after initial treatment of polypoidal choroidal vasculopathy using long-term follow-up data. METHODS: Retrospective study of 223 patients who were diagnosed with polypoidal choroidal vasculopathy and were followed up for up to 11 years. Subjects were categorized into "regression" and "no regression" groups, according to their polyp status after the initial treatment. Kaplan-Meier survival analyses were performed on development of massive SMH. The association between treatment methods and the occurrence of massive SMH was also analyzed. RESULTS: The incidence rates of massive SMH at 3, 6, and 9 years in the "no regression" group were 6.50, 22.59, and 38.03%, respectively, and in the "regression" group were 1.14, 6.47, and 10.92%, respectively (P = 0.005, log-rank test). The hazard ratio of massive SMH was 3.677 for cluster-type polyps and 0.271 for polyp regression after initial treatment. A higher rate of polyp regression was associated with photodynamic therapy (PDT) than anti-VEGF monotherapy (64.4 vs. 33.3%, P < 0.001). Additional anti-VEGF treatments after initial PDT showed lower risk of massive SMH than PDT only. (9.5 vs 38.5%, P = 0.005). CONCLUSION: The long-term risk of massive SMH after initial treatment on polypoidal choroidal vasculopathy is significantly higher in eyes with persistent polyps than those with regressed polyps. Ophthalmologists should pay attention to the risk of massive SMH and the polyp status when treating polypoidal choroidal vasculopathy.

Risk Factors and Outcomes of Choroidal Neovascularization Secondary to Central Serous Chorioretinopathy.

We identified clinical characteristics and risk factors of choroidal neovascularization (CNV) in eyes with prior episode of central serous chorioretinopathy (CSC). This retrospective case-control study included those initially diagnosed with CSC and developed CNV secondarily (Group 1, n = 16), those diagnosed with CNV in eyes of previous putative CSC (Group 2, n = 14), and those initially diagnosed with CSC, and did not develop CNV secondarily, as a control group for Group 1 (Group 3, n = 250). Clinical characteristics including treatment outcomes were assessed. Demographics and multimodal imaging at the time of CSC diagnosis of secondary CNV were compared between the groups to identify risk factors. Duration from diagnosis of CSC to development of CNV in Group 1 was 40.2 ± 42.0 months. Classic CNV was noted in 23 (76.7%) eyes. After treatment with intravitreal antiangiogenics with average of 4.9 times, visual acuity improved in Group 1 and Group 2 (p = 0.002). Multivariate analysis revealed that systemic hypertension, pigmentary changes, and double layer sign were associated with development of CNV secondary to CSC (p < 0.05). Hypertension, pigmentary changes, and double layer sign were independent risk factors for CNV secondary to CSC. The CNV's responded well to treatment, resulting in improved vision.

Five-year nationwide incidence of macular hole requiring surgery in Korea.

BACKGROUND/AIMS: To estimate the incidence and demographics of macular hole (MH) requiring surgery in Korea. METHODS: Patients who underwent surgery for MH in Korea from 2011 to 2015 with the diagnostic code for MH and the surgical code for vitrectomy were retrospectively identified using the Korean national health claims database. The average incidence rate of MH during the 5-year study period was estimated by applying the direct method of standardisation using the 2015 census data as a reference population. RESULTS: A total of 7301 patients with MH requiring surgery were identified. The average incidence of MH requiring surgery was 3.14 (95 % CI, 3.07 to 3.21) per 100 000 person-years . The incidence in women (4.29 per 100 000 person-years; 95% CI, 4.17 to 4.40) was significantly higher than that in men (2.00 per 100 000 person-years; 95% CI, 1.92 to 2.07; p<0.001). The incidence rate of MH increased exponentially with increasing age between the ages of 35 years and 69 years and was highest among patients aged 65-69 years. The female-to-male ratio for the incidence of MH was 2.15:1. CONCLUSIONS: This study represents the largest nationwide population-based investigation of the incidence of MH, using a database that covers the entire population of South Korea. MH is the disease of elderly peaked 70 years old and more common in women.

RETINAL ARTERY OCCLUSION AFTER INTRAVASCULAR PROCEDURES: Case Series and Literature Review.

PURPOSE: To evaluate clinical characteristics and possible mechanisms of retinal artery occlusion (RAO) after intravascular procedures. METHODS: This study is retrospective case series and literature review. Twenty-seven patients with intravascular procedure-associated RAO (10 new patients and 17 from previous reports) were divided into Groups 1 and 2 according to assumed etiology-dislodged and new emboli, respectively. Clinical features and etiology of RAO were analyzed. RESULTS: Branch and central RAO were observed in 17 (63%) and 10 (37%) patients, respectively, and 61.1% of patients exhibited final BCVA ≥20/40. Intravascular procedures were performed at the carotid artery (48.1%), heart (25.9%), carotid artery or heart (3.7%), brain (11.1%), scalp/glabella (7.4%), and thyroid (3.7%). Ratio of patients with immediate and delayed (≥24 hours after procedure) onset of RAO was 17 (63.0%):10 (37.0%). In Group 1 (n = 16), RAO was associated with dislodged plaques in the carotid artery (9; 56.3%), heart (6; 37.5%), or carotid artery/heart (1; 6.3%), and one patient each experienced acute brain infarction and contralateral branch retinal artery occlusion. In group 2 (n = 11), RAO was associated with new thrombi (6; 54.5%) or emboli (5; 45.5%), and one patient experienced ocular pain, ophthalmoplegia, and blepharoptosis. CONCLUSION: Intravascular procedures might result in RAO because of embolic plaques dislodged from the carotid artery or heart, or new thrombi or embolic materials migrating through collateral channels. Branch retinal artery occlusion was more frequent than central retinal artery occlusion after intravascular procedures, which resulted in relatively good visual outcomes. Patients should be informed about immediate or delayed presentation of RAO after intravascular procedures.

AGE, SEX, AND TIME-SPECIFIC TRENDS IN SURGICAL APPROACHES FOR RHEGMATOGENOUS RETINAL DETACHMENT: A Nationwide, Population-Based Study Using the National Claim Registry.

PURPOSE: To investigate the primary surgical approach for rhegmatogenous retinal detachment (RRD) according to age group, sex, and year in Korea. METHODS: We retrospectively identified patients from the national claims database who underwent primary surgery for RRD from 2007 to 2011 using the diagnostic code and surgical codes for RRD. Patients were categorized into three groups according to surgical treatment; scleral buckling, vitrectomy, and combined operation. We analyzed the frequency and proportion of primary surgical approach for RRD according to age group, sex, and year. RESULTS: Of 24,928 RRD patients, 11,372 (45.6%) patients underwent scleral buckling, 10,583 (42.5%) patients underwent vitrectomy, and 2,973 (11.9%) underwent a combined operation. Regression analysis showed that relative proportion of surgical approach had linear relationship with age; the percentage of patients undergoing vitrectomy increased by an average of 7.55% every 10 years (P < 0.001). This age-related trend was observed for both sexes. Scleral buckling tended to be preferred in younger patients (<45 years) and vitrectomy in older patients (≥45 years). Men tended to undergo vitrectomy significantly more than women in patients aged 15 years to 34 years. There was no consistent trend over time in the primary surgical approach during the study period. CONCLUSION: Age and sex of RRD patients influence the selection of primary surgical approaches. Young patients tend to undergo scleral buckling, whereas older patients tend to receive vitrectomy. Among young patients, men are more likely to undergo vitrectomy than women. No discernible trend over time was observed in the surgical approach over the 5-year study period.

Morphologic characteristics of the outer retina in cone dystrophy on spectral-domain optical coherence tomography.

PURPOSE: To investigate the morphologic changes in the outer retina of patients with cone dystrophy, using spectral-domain optical coherence tomography (SD-OCT). METHODS: The medical records of 15 cone dystrophy patients examined from January 2007 to January 2012 were reviewed retrospectively. All patients underwent ophthalmic evaluation including best-corrected visual acuity (BCVA), color vision testing, fundus examination, full-field standard electroretinography (ERG), multifocal (mf) ERG, and SD-OCT. Qualitative and quantitative SD-OCT data and ERG responses were analyzed and compared among the patient categories and the normal control group. RESULTS: There were 4 major categories of SD-OCT findings, based on the status of the ellipsoid portion of the photoreceptor inner segment (ISe), outer segment (OS) contact cylinder, and retinal pigment epithelium (RPE) layer. Category 0 showed no structural abnormalities. Category 1 showed foveal ISe loss and obscurity of the border between the ISe band and the external limiting membrane (ELM). Category 2 showed foveal thinning and focal foveal ISe disruption with an intact ELM. Category 3 showed foveal thickening and perifoveal disruption of the ISe layer. Category 1 to 3 showed OS contact cylinder layer absence and RPE thickening. The patients in category 0 tended to be younger (mean, 10.0 years) than those in categories 1 to 3 (mean, 17.6 years), although this difference was not statistically significant. Category 1 to 3 patients exhibited statistically significant thinning of the central retina and outer nuclear layer and thickening of the RPE layer relative to the category 0 and normal control group. There was a significant correlation between the central foveal thickness and BCVA in the patients with cone dystrophy. ERG and mfERG responses did not differ significantly among the different cone dystrophy categories. CONCLUSIONS: The morphologic features of cone dystrophy as revealed by SD-OCT, could be categorized as either normal or 1 of 3 different types of outer retinal changes. The presence of normal retinal structures in young cone dystrophy patients with functional impairment (category 0) indicates that electrophysiologic studies are superior to current imaging modalities for the early diagnosis of cone dystrophy. The characteristic SD-OCT findings in cone dystrophy patients may aid in differential diagnosis and be useful for future research on the pathology of cone dystrophy.